DESCRIPTION: (Applicant's Abstract) We propose a longitudinal study to monitor prefrontal cortical functioning in 56 heroin-dependent patients during the course of opiate maintenance. Using a newly developed variant of the Go/No Go task and functional magnetic resonance imaging (fMRI), we will assess whether prefrontal cortical activity increases with clinical improvement, both in dorsolateral regions associated with delay-dependent processing and in ventral areas associated with inhibitory processing. We will additionally use a combined fMRI/microdialysis system in a rat model to measure the neurochemical changes in those relevant brain areas identified in the clinical investigation. Heroin dependence remains a major public health problem in the United States. Opiate maintenance is the most effective treatment modality with an estimated 115,000 individuals currently receiving methadone maintenance (IOM Report, 1995). Despite its demonstrable effectiveness and widespread use, very little is known about the cognitive effects of chronic methadone. We know that opiate maintenance treatment allows opiate addicts to cease their relentless search for illicit opiates, accompanied by psychosocial stabilization in a number of domains including decreased criminal activity, increased productivity, increased employment and educational pursuits. Clinically, as the destabilized lifestyle of the addict is marked by impulsivity (by diagnostic definition), it appears apparent that clinical improvement must be accompanied by improvements in this cognitive characteristic. Opposition to opiate maintenance has always arisen from the view that opiate maintenance merely swaps one abused narcotic for another. From both a clinical and sociopolitical standpoint it is obviously relevant to establish that opiate maintenance treats a cognitive deficit induced by previous illicit opiate abuse. We have found no study addressing whether and how opiate maintenance affects impulsivity.